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1.
Transl Vis Sci Technol ; 11(11): 10, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36374486

RESUMO

Purpose: The purpose of this study was to determine whether rodent lacrimal glands (LGs) represent a suitable surrogate for human tissue in bio-engineering research, we undertook a meticulous histological and histochemical comparison of these two tissues. Methods: Histological techniques and immunohistochemistry were used to compare the structure of adult human and rat LG tissues and the expression of key functional tissue elements. Results: Compared with humans, the rat LG is comprised of much more densely packed acini which are devoid of an obvious central lumen. Myoepithelial, fibroblasts, dendritic cells, T cells, and putative progenitor cells are present in both tissues. However, human LG is replete with epithelium expressing cytokeratins 8 and 18, whereas rat LG epithelium does not express cytokeratin 8. Furthermore, human LG expresses aquaporins (AQPs) 1, 3, and 5, whereas rat LG expresses AQPs 1, 4, and 5. Additionally, mast cells were identified in the rat but not the human LGs and large numbers of plasma cells were detected in the human LGs but only limited numbers were present in the rat LGs. Conclusions: The cellular composition of the human and rat LGs is similar, although there is a marked difference in the actual histo-architectural arrangement of the tissue. Further variances in the epithelial cytokeratin profile, in tissue expression of AQPs and in mast cell and plasma cell infiltration, may prove significant. Translational Relevance: The rat LG can serve as a useful surrogate for the human equivalent, but there exist specific tissue differences meaning that caution must be observed when translating results to patients.


Assuntos
Aquaporinas , Aparelho Lacrimal , Humanos , Adulto , Ratos , Animais , Aparelho Lacrimal/química , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Células-Tronco , Aquaporinas/análise , Aquaporinas/metabolismo , Epitélio , Bioengenharia
2.
Plant Physiol Biochem ; 193: 25-35, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36323195

RESUMO

Aquaporins are water channel proteins that play an essential role in plant growth and development. Despite extensive functional characterization of aquaporins in model plants such as Arabidopsis, their contributions to abiotic stress tolerance in non-model plants are still poorly understood. As a close relative of Arabidopsis thaliana, Eutrema salsugineum is an excellent model for studying salt tolerance. Here, we identified and functionally characterized EsPIP1;4, a gene encoding a plasma membrane intrinsic protein (PIP) aquaporin in E. salsugineum. Overexpression of EsPIP1;4 in Arabidopsis improved seed germination and root growth of transgenic plants under abiotic stress, which was accompanied by an increase in proline accumulation, reduction in MDA, and decrease in the rate of ion leakage. Under abiotic stress, transgenic plants overexpressing EsPIP1;4 also showed increased antioxidant enzyme activity, and enhanced K+/Na+ ratio compared to control plants. Furthermore, overexpression of EsPIP1;4 promoted flowering by regulating genes in multiple flowering pathways. Together, our results demonstrated that an aquaporin from E. salsugineum improves abiotic stress tolerance and promotes flowering.


Assuntos
Aquaporinas , Arabidopsis , Arabidopsis/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Cell Mol Life Sci ; 79(12): 592, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36378343

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that is crucial for fluid homeodynamics throughout the male reproductive tract. Previous evidence shed light on a potential molecular partnership between this channel and aquaporins (AQPs). Herein, we explore the role of CFTR on AQPs-mediated glycerol permeability in mouse Sertoli cells (mSCs). We were able to identify the expression of CFTR, AQP3, AQP7, and AQP9 in mSCs by RT-PCR, Western blot, and immunofluorescence techniques. Cells were then treated with CFTRinh-172, a specific CFTR inhibitor, and its glycerol permeability was evaluated by stopped-flow light scattering. We observed that CFTR inhibition decreased glycerol permeability in mSCs by 30.6% when compared to the control group. A DUOLINK proximity ligation assay was used to evaluate the endogenous protein-protein interactions between CFTR and the various aquaglyceroporins we identified. We positively detected that CFTR is in close proximity with AQP3, AQP7, and AQP9 and that, through a possible physical interaction, CFTR can modulate AQP-mediated glycerol permeability in mSCs. As glycerol is essential for the control of the blood-testis barrier and elevated concentration in testis results in the disruption of spermatogenesis, we suggest that the malfunction of CFTR and the consequent alteration in glycerol permeability is a potential link between male infertility and cystic fibrosis.


Assuntos
Aquaporinas , Glicerol , Camundongos , Animais , Masculino , Glicerol/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Células de Sertoli/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Permeabilidade
4.
Metab Brain Dis ; 37(8): 2777-2782, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36214979

RESUMO

Cadmium (Cd) is a toxicant metal that risks human and animal health. Nowadays, the vital role of Aquaporin-4 (AQP-4) in brain and gut cell permeability has gathered too much attention to protecting against heavy metals. Studies have shown that heavy metals can harm the body due to oxidative stress. Probiotics are known for their health-beneficial effects and establish as dietary adjuncts mainly for their antioxidant properties. This study investigated the impact of a novel probiotic combination including Lactobacillus casei IBRC-M10783, Lactobacillus rhamnosus IBRC-M10782, and Lactobacillus helveticus TG-34 on the AQP-4 gene expression in CdCl2-induced Wistar rats. Rats were divided into three groups and received a specific dose of CdCl2 or probiotics. The AQP-4 expression level had estimated by Real-Time PCR in both the intestine and brain. These results showed a significant reduction in AQP-4 gene expression in the probiotic treatment group compared to the CdCl2 control group in the intestine and brain for the first time. Our research showed that consuming a probiotic mixture of L. casei, L. rhamnosus, and L. helveticus can reduce the expression of the aquaporin-4 gene in the brain and intestine of rats exposed to Cadmium, which can be promising in the field of aquaporin-4 regulation.


Assuntos
Aquaporinas , Metais Pesados , Probióticos , Humanos , Ratos , Animais , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Ratos Wistar , Probióticos/farmacologia , Probióticos/uso terapêutico , Metais Pesados/metabolismo , Metais Pesados/farmacologia , Intestinos , Encéfalo/metabolismo , Expressão Gênica , Aquaporinas/metabolismo , Aquaporinas/farmacologia
5.
Life Sci Alliance ; 5(12)2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229063

RESUMO

Aquaporins are protein channels embedded in the lipid bilayer in cells from all organisms on earth that are crucial for water homeostasis. In fish, aquaporins are believed to be important for osmoregulation; however, the molecular mechanism behind this is poorly understood. Here, we present the first structural and functional characterization of a fish aquaporin; cpAQP1aa from the fresh water fish climbing perch (<i>Anabas testudineus</i>), a species that is of high osmoregulatory interest because of its ability to spend time in seawater and on land. These studies show that cpAQP1aa is a water-specific aquaporin with a unique fold on the extracellular side that results in a constriction region. Functional analysis combined with molecular dynamic simulations suggests that phosphorylation at two sites causes structural perturbations in this region that may have implications for channel gating from the extracellular side.


Assuntos
Aquaporinas , Bicamadas Lipídicas , Animais , Aquaporinas/química , Aquaporinas/metabolismo , Água Doce , Água do Mar , Água/metabolismo
6.
Genes Genomics ; 44(12): 1457-1469, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36239846

RESUMO

BACKGROUND: Nile tilapia (Oreochromis niloticus), an important economic freshwater fish being cultured globally, is highly adaptable to a wide range of salinities. However, little information is currently available on the mechanism of salinity adaptation. OBJECTIVE: For a better understanding of this intriguing adaptability, we identified and analyzed aquaporins (AQPs), which are channel proteins with a basic function of intracellular and intercellular transportation for water and certain solutes. METHODS: In the present study, we performed genome-wide identification and comprehensive analysis of the duplicated AQP genes in Nile tilapia by bioinformatics methods. Tissue-specific analyses were then combined with transcriptome data under different salinity treatments. RESULTS: It was revealed that Nile tilapia has a total of twenty-eight AQPs, which are distributed unevenly on twelve chromosomes and belong to four subfamilies according to phylogenetic analysis. These AQPs share conserved AQP characteristic structural domains and motifs, although they differ in molecular weight from 23 to 36 kDa and contain distinct sequences. GO analysis revealed that most AQPs have transporter protein activity and are involved in biological processes such as substance transport, stress response, development and metabolism. KEGG enrichment analysis showed that AQPs were significantly enriched in two pathways, anti-diuretic hormone-regulated reabsorption and bile secretion. CONCLUSION: These results suggested that Nile tilapia has a highly developed, albeit complex, osmotic pressure regulation system, which provided a molecular basis for exploring how these AQP members coordinate to help Nile tilapia cope with different salinities.


Assuntos
Aquaporinas , Ciclídeos , Animais , Ciclídeos/genética , Ciclídeos/metabolismo , Salinidade , Filogenia , Aquaporinas/genética , Aquaporinas/metabolismo , Transcriptoma
7.
Int J Mol Sci ; 23(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36293538

RESUMO

Tonoplast intrinsic proteins (TIPs), a sub-family of aquaporins (AQPs), are known to play important roles in plant abiotic stress responses. However, evidence for the promoters of TIPs involvement in abiotic stress processes remains scarce. In this study, the promoter of the vegetable soybean GmTIP1;6 gene, which had the highest similarity to TIP1-type AQPs from other plants, was cloned. Expression pattern analyses indicated that the GmTIP1;6 gene was dramatically induced by drought, salt, abscisic acid (ABA), and methyl jasmonate (MeJA) stimuli. Promoter analyses revealed that the GmTIP1;6 promoter contained drought, ABA, and MeJA cis-acting elements. Histochemical staining of the GmTIP1;6 promoter in transgenic Arabidopsis corroborated that it was strongly expressed in the vascular bundles of leaves, stems, and roots. Beta-glucuronidase (GUS) activity assays showed that the activities of the GmTIP1;6 promoter were enhanced by different concentrations of polyethylene glycol 6000 (PEG 6000), NaCl, ABA, and MEJA treatments. Integrating these results revealed that the GmTIP1;6 promoter could be applied for improving the tolerance to abiotic stresses of the transgenic plants by promoting the expression of vegetable soybean AQPs.


Assuntos
Aquaporinas , Arabidopsis , Fabaceae , Arabidopsis/metabolismo , Soja/genética , Soja/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Verduras/metabolismo , Regulação da Expressão Gênica de Plantas , Cloreto de Sódio/farmacologia , Estresse Fisiológico , Plantas Geneticamente Modificadas/metabolismo , Secas , Aquaporinas/metabolismo , Fabaceae/metabolismo , Hormônios/metabolismo , Glucuronidase/genética , Glucuronidase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
Nutrients ; 14(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36235735

RESUMO

Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae_RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.


Assuntos
Constipação Intestinal , Lactobacillus salivarius , Loperamida , Serotonina , Animais , Aquaporinas/metabolismo , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/prevenção & controle , Loperamida/efeitos adversos , Camundongos , Serotonina/metabolismo , Transdução de Sinais , Somatostatina/metabolismo , Substância P/metabolismo , Triptofano Hidroxilase/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo
9.
Cells ; 11(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36231080

RESUMO

Aquaporin-9 (AQP9) is a facilitator of glycerol and other small neutral solute transmembrane diffusion. Identification of specific inhibitors for aquaporin family proteins has been difficult, due to high sequence similarity between the 13 human isoforms, and due to the limited channel surface areas that permit inhibitor binding. The few AQP9 inhibitor molecules described to date were not suitable for in vivo experiments. We now describe the characterization of a new small molecule AQP9 inhibitor, RG100204 in cell-based calcein-quenching assays, and by stopped-flow light-scattering recordings of AQP9 permeability in proteoliposomes. Moreover, we investigated the effects of RG100204 on glycerol metabolism in mice. In cell-based assays, RG100204 blocked AQP9 water permeability and glycerol permeability with similar, high potency (~5 × 10-8 M). AQP9 channel blocking by RG100204 was confirmed in proteoliposomes. After oral gavage of db/db mice with RG100204, a dose-dependent elevation of plasma glycerol was observed. A blood glucose-lowering effect was not statistically significant. These experiments establish RG100204 as a direct blocker of the AQP9 channel, and suggest its use as an experimental tool for in vivo experiments on AQP9 function.


Assuntos
Aquaporinas , Glicerol , Animais , Aquaporinas/metabolismo , Glicemia/metabolismo , Glicerol/metabolismo , Glicerol/farmacologia , Humanos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos , Água/metabolismo
10.
Anal Biochem ; 659: 114934, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36206845

RESUMO

Intestinal epithelial cells (IECs) are an important point of contact between dietary food components consumed and subsequent whole-body utilization for body maintenance and growth. Selective bioactive phenolic acids, widely present in fruits, vegetables and beverages can generate hydrogen peroxide (H2O2) and contribute to the cellular redox balance, hence influencing well-known cellular antioxidant and pro-oxidant mechanisms. Our findings have showed that increasing extracellular H2O2 resulted in associated changes in intracellular H2O2 levels in Caco-2 cells (p < 0.05) which was facilitated by activity of a family of water channel membrane proteins, termed aquaporins (AQPs). To demonstrate this, a HyPer-3 genetically encoded fluorescent H2O2 sensitive indicator was used to enable fluorescent real-time imaging of intracellular H2O2 levels as a measure of changes occurring in extracellular H2O2 in differentiated Caco-2 cells exposed to different phenolic acids. The use of confocal microscopy and flow cytometry, respectively, captured visualization and quantification of H2O2 uptake in differentiated Caco-2 cells. DFP00173, an aquaporin 3 (AQP3) inhibitor was effective at inhibiting the intracellular uptake of H2O2 and was sensitive to varied levels of H2O2 generated when different phenolic acids were added to the culture media. In summary, HyPer-3 was shown to be an effective technique to demonstrate relative capabilities of structurally different dietary phenolic acids that have potential to alter intestinal redox balance by changing intracellular H2O2, and either antioxidant or pro-oxidant activity, respectively.


Assuntos
Aquaporinas , Peróxido de Hidrogênio , Humanos , Peróxido de Hidrogênio/metabolismo , Células CACO-2 , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Aquaporinas/metabolismo
11.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293145

RESUMO

Hypertension is the leading cause of cardiovascular affection and premature death worldwide. The spontaneously hypertensive rat (SHR) is the most common animal model of hypertension, which is characterized by secondary ventricular dilation and hydrocephalus. Aquaporin (AQP) 1 and 4 are the main water channels responsible for the brain's water balance. The present study focuses on defining the expression of AQPs through the time course of the development of spontaneous chronic hypertension. We performed immunofluorescence and ELISA to examine brain AQPs from 10 SHR, and 10 Wistar-Kyoto (WKY) rats studied at 6 and 12 months old. There was a significant decrease in AQP1 in the choroid plexus of the SHR-12-months group compared with the age-matched control (p < 0.05). In the ependyma, AQP4 was significantly decreased only in the SHR-12-months group compared with the control or SHR-6-months groups (p < 0.05). Per contra, AQP4 increased in astrocytes end-feet of 6 months and 12 months SHR rats (p < 0.05). CSF AQP detection was higher in the SHR-12-months group than in the age-matched control group. CSF findings were confirmed by Western blot. In SHR, ependymal and choroidal AQPs decreased over time, while CSF AQPs levels increased. In turn, astrocytes AQP4 increased in SHR rats. These AQP alterations may underlie hypertensive-dependent ventriculomegaly.


Assuntos
Aquaporinas , Hidrocefalia , Hipertensão , Animais , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Aquaporina 1/metabolismo , Encéfalo/metabolismo , Hidrocefalia/metabolismo , Hipertensão/metabolismo , Água/metabolismo , Aquaporina 4/metabolismo , Aquaporinas/metabolismo
12.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293170

RESUMO

Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time.


Assuntos
Aquaporinas , Aquaporinas/metabolismo , Simulação de Dinâmica Molecular , Água/metabolismo , Biofísica , Permeabilidade da Membrana Celular
13.
Int J Mol Sci ; 23(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36293210

RESUMO

Women are more prone to develop either hypothyroidism or cholesterol gallstones than men. However, a male predominance in cholesterol gallstones under hypothyroidism was reported. Recently, a novel pathogenic link between thyroid hormone (TH) deficiency and cholesterol gallstones has been described in male mice. Here, we investigate if TH deficiency impacts cholesterol gallstone formation in females by the same mechanism. Three-month-old C57BL/6J mice were randomly divided into a control, a TH deficient, a lithogenic, and a lithogenic + TH deficient group and diet-treated for two, four, and six weeks. Gallstone prevalence, liver function tests, bile composition, hepatic gene expression, and gallbladder aquaporin expression and localization were investigated. Cholesterol gallstones were observed in lithogenic + TH deficient but not lithogenic only female mice. Diminished hydrophilicity of primary bile acids due to decreased gene expression of hepatic detoxification phase II enzymes was observed. A sex-specific expression and localization of hepatobiliary aquaporins involved in transcellular water and glycerol permeability was observed under TH deficient and lithogenic conditions. TH deficiency promotes cholesterol gallstone formation in female C57BL/6J mice by the same mechanism as observed in males. However, cholesterol gallstone prevalence was lower in female than male C57BL/6J mice. Interestingly, the sex-specific expression and localization of hepatobiliary aquaporins could protect female C57BL/6J mice to cholestasis and could reduce biliary water transport in male C57BL/6J mice possibly contributing to the sex-dependent cholesterol gallstone prevalence under TH deficiency.


Assuntos
Aquaporinas , Colestase , Cálculos Biliares , Hipotireoidismo , Feminino , Masculino , Camundongos , Animais , Ácidos e Sais Biliares/metabolismo , Camundongos Endogâmicos C57BL , Cálculos Biliares/genética , Cálculos Biliares/metabolismo , Cálculos Biliares/patologia , Glicerol/metabolismo , Colesterol/metabolismo , Fígado/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Colestase/metabolismo , Ácido Cólico/metabolismo , Hipotireoidismo/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Hormônios Tireóideos/metabolismo , Água/metabolismo
14.
Int J Mol Sci ; 23(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36233096

RESUMO

Plasma membrane intrinsic protein (PIP) is one of the largest subfamilies of Aquaporins (AQPs) and plays an important role in plant growth and development, and resistance to abiotic stress. In this study, the full length of the EuPIP1;1 cDNA was cloned from Eucommia ulmoides using the rapid amplification of cDNA ends (RACE) method. The EuPIP1;1 gene was induced by drought treatment and expressed in all tested tissues, with the highest expression level in fruit. The subcellular localization showed that EuPIP1;1 was located in the plasma membrane. Constitutive overexpression of EuPIP1;1 in Arabidopsisthaliana could promote leaf growth and development, and accelerate bolting and flowering. Six genes related to growth and flowering (AtPIF4, AtTCP14, AtCRY1, AtCRY2, AtFCA and AtFT) were significantly up-regulated in transgenic lines. Further, EuPIP1;1 gene improved resistance to drought and salt stress in transgenic Arabidopsis. Under drought and salt stress treatment, the transgenic lines had a higher germination rate and accumulation of osmotic substances, lower membrane damage, and could maintain ion homeostasis. Our results suggest that EuPIP1;1 plays an essential role in plant growth and development and in the response to drought and salt stress.


Assuntos
Aquaporinas , Arabidopsis , Eucommiaceae , Aquaporinas/genética , Aquaporinas/metabolismo , Arabidopsis/metabolismo , DNA Complementar/metabolismo , Secas , Eucommiaceae/genética , Regulação da Expressão Gênica de Plantas , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal/genética , Estresse Fisiológico/genética
16.
Neurotox Res ; 40(5): 1337-1347, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057040

RESUMO

Methylglyoxal (MG) is a reactive dicarbonyl compound formed mostly via the glycolytic pathway. Elevated blood glucose levels can cause MG accumulation in plasma and cerebrospinal fluid in patients with diabetes mellitus and Alzheimer's disease. Under these disease conditions, the high reactivity of MG leads to modification of proteins and other biomolecules, generating advanced glycation end products (AGEs), which are considered mediators in neurodegenerative diseases. We investigated the integrity of the blood-brain barrier (BBB) and astrocyte response in the hippocampus to acute insult induced by MG when it was intracerebroventricularly administered to rats. Seventy-two hours later, BBB integrity was lost, as assessed by the entry of Evans dye into the brain tissue and albumin in the cerebrospinal fluid, and a decrease in aquaporin-4 and connexin-43 in the hippocampal tissue. MG did not induce changes in the hippocampal contents of RAGE in this short interval, but decreased the expression of S100B, an astrocyte-secreted protein that binds RAGE. The expression of two important transcription factors of the antioxidant response, NF-κB and Nrf2, was unchanged. However, hemeoxigenase-1 was upregulated in the MG-treated group. These data corroborate the idea that hippocampal cells are targets of MG toxicity and that BBB dysfunction and specific glial alterations induced by this compound may contribute to the behavioral and cognitive alterations observed in these animals.


Assuntos
Aquaporinas , Aldeído Pirúvico , Albuminas/metabolismo , Animais , Antioxidantes/metabolismo , Aquaporinas/metabolismo , Glicemia/metabolismo , Barreira Hematoencefálica/metabolismo , Conexinas/metabolismo , Produtos Finais de Glicação Avançada/toxicidade , Hipocampo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Aldeído Pirúvico/farmacologia , Ratos , Receptor para Produtos Finais de Glicação Avançada/metabolismo
17.
Int J Mol Sci ; 23(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36077012

RESUMO

Aquaporins (AQPs) are a family of transmembrane water channels expressed in all living organisms. AQPs facilitate osmotically driven water flux across biological membranes and, in some cases, the movement of small molecules (such as glycerol, urea, CO2, NH3, H2O2). Protein-protein interactions play essential roles in protein regulation and function. This review provides a comprehensive overview of the current knowledge of the AQP interactomes and addresses the molecular basis and functional significance of these protein-protein interactions in health and diseases. Targeting AQP interactomes may offer new therapeutic avenues as targeting individual AQPs remains challenging despite intense efforts.


Assuntos
Aquaporinas , Peróxido de Hidrogênio , Animais , Aquaporinas/metabolismo , Peróxido de Hidrogênio/metabolismo , Mamíferos/metabolismo , Ureia/metabolismo , Água/metabolismo
18.
J Mol Graph Model ; 117: 108310, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36063744

RESUMO

Aquaporins are an ancient family of membrane channel proteins present in all eukaryotes and most prokaryotes, and apart from water, allow the transport of neutral solutes and organic compounds through the pore. These proteins are essential role differentially expressed during ripening in Fragaria vesca fruits. Fv PIP2-1a is intensively expressed in fruits, inclusive several other proteins member are differentially expressed in fruit but also in other plant tissues. Phylogenetic analysis shows that Fv PIP2-1a grouped with other Fragaria proteins and far apart from other F. vesca PIP proteins. A structural model for Fv PIP2-1a protein was built by comparative modelling methodology, which was validated and refined by molecular dynamics simulation. Fv PIP2-1a structure consists of 6 transmembrane regions and two NPA domains. The mobilization of water was analyzed by molecular docking simulations in wildtype and two mutants. Interestingly, the mutant FvPIP2-1a_H214G allowed the prediction of an increment in the flux of water molecules. On contrary, structural analysis predicted that H214E mutation blocked passage of water associated to constriction of the pore.


Assuntos
Aquaporinas , Fragaria , Aquaporinas/genética , Aquaporinas/metabolismo , Fragaria/genética , Fragaria/metabolismo , Simulação de Acoplamento Molecular , Filogenia , Proteínas de Plantas/química , Água/metabolismo
19.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142747

RESUMO

Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H2O2), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H2O2, and thus ROS scavenging, appears particularly important for controlling the redox state of cells in physiological and pathophysiological conditions. Several compounds have been screened and characterized for this purpose. This study aimed to analyze the effect of cerium oxide nanoparticles (CNPs) presenting antioxidant activity on AQP functioning. HeLa cells express AQP3, 6, 8, and 11, able to facilitate H2O2. AQP3, 6, and 8 are expressed in the plasma membrane and intracellularly, while AQP11 resides only in intracellular structures. CNPs but not cerium ions treatment significantly increased the water and H2O2 permeability by interacting with AQP3, 6, and especially with AQP8. CNPs increased considerably the AQP-mediated water diffusion in cells with oxidative stress. Functional experiments with silenced HeLa cells revealed that CNPs increased the H2O2 diffusion mainly by modulating the AQP8 permeability but also the AQP3 and AQP6, even if to a lesser extent. Current findings suggest that CNPs represent a promising pharmaceutical agent that might potentially be used in numerous pathologies involving oxidative stress as tumors and neurodegenerative diseases.


Assuntos
Aquaporinas , Nanopartículas , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Aquaporinas/metabolismo , Cério , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Permeabilidade , Espécies Reativas de Oxigênio/metabolismo , Água/metabolismo
20.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077217

RESUMO

In this study, a first experiment was conducted with the objective of determining how drought stress alters the radial water flow and physiology in the whole maize nested association mapping (NAM) population and to find out which contrasting maize lines should be tested in a second experiment for their responses to drought in combination with an arbuscular mycorrhizal (AM) fungus. Emphasis was placed on determining the role of plant aquaporins and phytohormones in the responses of these contrasting maize lines to cope with drought stress. Results showed that both plant aquaporins and hormones are altered by the AM symbiosis and are highly involved in the physiological responses of maize plants to drought stress. The regulation by the AM symbiosis of aquaporins involved in water transport across cell membranes alters radial water transport in host plants. Hormones such as IAA, SA, ABA and jasmonates must be involved in this process either by regulating the own plant-AM fungus interaction and the activity of aquaporins, or by inducing posttranscriptional changes in these aquaporins, which in turns alter their water transport capacity. An intricate relationship between root hydraulic conductivity, aquaporins and phytohormones has been observed, revealing a complex network controlling water transport in maize roots.


Assuntos
Aquaporinas , Micorrizas , Aquaporinas/metabolismo , Secas , Hormônios/metabolismo , Micorrizas/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Simbiose/fisiologia , Água/metabolismo , Zea mays/metabolismo
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